In recent years, we have defined several classes of human cancer cell surface antigens by an approach we refer to as autologous serological typing. An important current question is whether melanoma cell surface antigens detected by serological tests and tests for cell-mediated cytotoxicity (CMC) are the same. We propose here to examine the specificity of cell surface antigens recognized by cytotoxic T cells on cultured autologous human melonoma cells in parallel with our ongoing serological analysis of melanoma cell surface antigens. Essential steps in our proposal are (1) the preparation of T cells cytotoxic for autologous cultured melanoma cells from the peripheral blood, lymph nodes and tumor tissue of melanoma patients, (2) expansion of cytotoxic T cell populations by culture in TCGF, (3) cloning of cultured cytotoxic T cells and developmnt of cloned cell lines, (4) definition of the specificity of melanoma cell surface antigens recognized by cloned cytotoxic T cell lines using direct tests, competetive inhibition, cellular immunoadsorption and antibody blocking, and (5) definition of the cell surface phenotype of the cloned cytotoxic T cell lines. While this proposal is exclusively for the study of cell-mediated immunity, our ongoing serological analysis of the cell surface antigens of malignant melanoma will contribute much to its successful pursuit.